Aqueous ophthalmic solutions of phentolamine and medical uses thereof

Abstract

The invention provides aqueous ophthalmic solutions of phentolamine or pharmaceutically acceptable salts thereof, medical kits, and methods for using such ophthalmic solutions to improve visual performance in a patient. Exemplary aqueous ophthalmic solutions include those containing phentolamine mesylate, mannitol, sodium acetate, and water.

The invention claimed is: 
     
       1. An aqueous ophthalmic solution, consisting of:
 a. about 0.1% (w/v) to about 4% (w/v) of phentolamine or a pharmaceutically acceptable salt thereof; 
 b. about 1% (w/v) to about 6% (w/v) of at least one polyol compound selected from the group consisting of mannitol, glycerol, propylene glycol, ethylene glycol, sorbitol, and xylitol; 
 c. about 0.1 mM to about 10 mM of at least one buffer; 
 d. water; and 
 e. optionally one or more of a poly (C 2-4 alkylene) glycol polymer, dextran, cellulose agent, carbohydrate, alkali metal halide, alkaline earth metal halide, boric acid, cyclodextrin, dextrose, glycerin, urea, preservative, viscosity modifying agent, solubilizing agent, surfactant, demulcent polymer, wetting agent, or water-miscible solvent; 
 wherein the solution has a pH in the range of 4.0 to 7.5. 
 
     
     
       2. The solution of  claim 1 , wherein the at least one polyol compound is mannitol. 
     
     
       3. The solution of  claim 1 , wherein the solution has from about 2% (w/v) to about 5% (w/v) of the at least one polyol compound. 
     
     
       4. The solution  claim 1 , wherein the solution has from about 3.5% (w/v) to about 4.5% (w/v) of the at least one polyol compound. 
     
     
       5. The solution of  claim 1 , wherein the solution has about 4% (w/v) of the at least one polyol compound. 
     
     
       6. The solution of  claim 1 , wherein the buffer is present at a concentration in the range of about 2 mM to about 4 mM. 
     
     
       7. The solution of  claim 1 , wherein the buffer is present at a concentration of about 3 mM. 
     
     
       8. The solution of  claim 1 , wherein the buffer comprises an alkali metal acetate. 
     
     
       9. The solution of  claim 1 , wherein the buffer comprises sodium acetate. 
     
     
       10. The solution of  claim 1 , wherein the solution has a pH in the range of 4.5 to 6.0. 
     
     
       11. The solution of  claim 1 , wherein the solution has a pH in the range of 4.7 to 5.1. 
     
     
       12. The solution of  claim 1 , wherein the solution has from about 0.5% (w/v) to about 2% (w/v) of phentolamine or a pharmaceutically acceptable salt thereof. 
     
     
       13. The solution of  claim 1 , wherein the solution has about 1% (w/v) of phentolamine or a pharmaceutically acceptable salt thereof. 
     
     
       14. The solution of  claim 1 , wherein the solution consists of:
 a. about 0.25% (w/v) to about 2% (w/v) of phentolamine mesylate; 
 b. about 1% (w/v) to about 6% (w/v) of at least one polyol compound selected from the group consisting of mannitol, glycerol, propylene glycol, ethylene glycol, sorbitol, and xylitol; 
 c. about 0.1 mM to about 10 mM of at least one buffer; 
 d. water; and 
 e. optionally one or more of a poly (C 2-4 alkylene) glycol polymer, dextran, alkali metal halide, alkaline earth metal halide, boric acid, or preservative. 
 
     
     
       15. The solution of  claim 1 , wherein the solution has from about 0.25% (w/v) to about 1% (w/v) of phentolamine mesylate. 
     
     
       16. The solution of  claim 1 , wherein the solution has about 1% (w/v) of phentolamine mesylate. 
     
     
       17. The solution of  claim 2 , wherein the solution has from about 3.5% (w/v) to about 4.5% (w/v) of the at least one polyol compound. 
     
     
       18. The solution of  claim 17 , wherein the buffer comprises an alkali metal acetate. 
     
     
       19. The solution of  claim 17 , wherein the buffer comprises sodium acetate. 
     
     
       20. The solution of  claim 19 , wherein the buffer is present at a concentration in the range of about 2 mM to about 4 mM. 
     
     
       21. The solution of  claim 20 , wherein the solution has a pH in the range of 4.5 to 6.0. 
     
     
       22. The solution of  claim 21 , wherein the solution has from about 0.25% (w/v) to about 2% (w/v) of phentolamine mesylate. 
     
     
       23. The solution of  claim 21 , wherein the solution has about 1% (w/v) of phentolamine mesylate.